Charged lipids

FIGURE 6-15 Schematic representation of the ion permeability modulation for cation-responsive voltammetric sensors based on negatively charged lipid membranes. Complexation of the guest cation to the phospholipid receptors causes an increase of the permeability for the anionic marker ion. (Reproduced with permission from reference 49.)... 

The actual characteristics of REV produced depend on a number of factors such as choice of lipids (% cholesterol and charged lipids), lipid concentration used in the organic solvent, rate of evaporation, and ionic strength of the aqueous phase (Szoka and Papahadjopoulos, 1980). Modifications of this REV technique were proposed by several groups. The SPLV (stable plurilamellar vesicles) method consists of bath-sonicating an emulsion of the aqueous phase in an ether solution of lipid while evaporating the ether (Griiner et al., 1985). 

Six two-component models were tested under sink conditions (models 5.1-10.1 in Table 7.3), employing three negatively charged lipids (dodecylcarboxylic acid, phosphatidic acid, and phosphatidylglycerol). These models were also tested in the absence of the sink condition (models 5.0-10.0 in Table 7.3). 

The negative-charge lipid content in the egg lecithins is not as high as that found in BBM and especially BBB lipids (Table 7.1). Furthermore, the negative-charge content in the egg lecithin is about one-fourth that in the soy lecithin. This is clearly evident in the membrane retention parameters for the bases at the 10% lecithin levels (models 12.0 or 14.0 in Table 7.8 vs. model 16.0 in Table 7.12), as they are 20-30% lower for the lipophilic bases in egg, compared to soy. 

The GIT has about 13% wt/wt negatively charged lipid-to-zwitterionic phospholipid ratio. It is about twice as large in the BBB. Factoring this into the in vitro model is expected to be important. 

Figure 3.6 compares iso-pH permeabilities of ketoprofen at various pH values in a 2% DOPC-dodecane model (open circles) and the 20% soy lecithin with SLS in the acceptor compartment (filled circles, data in Table 3.5). In the presence of the latter negatively charged lipids (with the make-up similar to that of BBM in Table 3.1), ketoprofen is intrinsically more permeable, by a factor of 17. The UWL limit, indicated by the solid curves in low-pH solutions, and consistent with the permeability Pu 19.8 x 10-6 cm s 1 (log Pu —4.7), masks the true intrinsic permeability of the membranes, P0. However, it is possible to deduce the membrane permeability if the pKa is known. In Fig. 3.6, the bending in the dashed (calculated) curves at pH 4 corresponds to the pKa of the molecule. Due to the UWL, the point of bending is shifted to higher pH values in the solid (measured) curves. The difference between the apparent pKa (pK 5.3 for DOPC and 6.3 for soy) and the true pKa (4.12) is the same as the difference between log P0 and log Pu [23],... 

The organization of lipids around the plasma membrane Ca2+-transport ATPase of erythrocytes has been also determined by FRET. Taking advantage of the intrinsic fluorescence of the ATPase due to tryptophan residues and labeling different types of lipids with pyrene, it was demonstrated that the transporter is preferentially surrounded by negatively charged lipids such as phosphoinositides [167],... 

The MBPs are extrinsic proteins localized exclusively at the cytoplasmic surface in the major dense line (Fig. 4-11), a conclusion based on their amino acid sequence, inaccessibility to surface probes and direct localization at the electron microscope level by immunocytochemistry. There is evidence to suggest that MBP forms dimers, and it is believed to be the principal protein stabilizing the major dense line of CNS myelin, possibly by interacting with negatively charged lipids. A severe hypomyelination and failure of compaction of the major dense line in MBP deficient shiverer mutants supports this hypothesis (Table 4-2). 

If charged lipids are incorporated in the membrane phase (indicated by subscript m) or if charged species are sorbed to the membrane surface, an electrochemical potential jlim will build up according to ... 

Figure 7. Lipophilicity profile of propranolol in liposomes composed of zwitterionic and charged lipids (phosphatidyl ethanolamine (PE), oleic acid (OA), phosphatidyl inositol (PI)). Conditions of measurements are described in [113]. The dotted line indicates the partitioning profile of propranolol in the egg PC liposome system. The bars show the pH-dependent charge profile of propranolol (hatched bars positively charged propranolol) and the lipids in the membrane (black bars negatively charged lipids). Reprinted from [113] Kramer, S. (2001). Liposome/water partitioning , In Pharmacokinetic Optimization in Drug Research, eds. Testa, B. et al. Reproduced by permission of Verlag Helvetica Chimica Acta, Zurich...

Tsui, F.C., Sundberg, S.A. and Hubbell, W.L., 1990, Distribution of charge on photoreceptor disc membranes and implications for charged lipid asymmetry. Biophys. J. 57 85-97. 

The ratio of the two phospholipids also affected the absorbance and CD spectra. In particular, a high proportion of the negatively charged lipid DMPG led to an inversion of the dichroic doublet, suggesting a drastic change in AmB organization. 

PS (anionic) or 4 nmol of SA, BisHOP, DOTMA, DOTAP, DODAB, or DC-CHOL (cationic) are also added (molar ratio 4 2 1). For cationic man-nosylated liposomes, 4 pmol of DOGP-4 a Man was included at the molar ratio of 4 2 1 1. Greater amounts of charged lipids can be added depending on the amount of vesicle surface charge required. 

In this section, an example will be given in which a (small) library of a new type of cationic lipids was synthesized and screened for TE (63). For synthesis, combinatorial solid phase chemistry was used. All cationic lipids of the example library are structurally based on 3-methylamino-1,2-dihydroxy-propane as the polar, cationic lipid part. As nonpolar lipid part, different hydrocarbon chains are boimd to the amino group of the scaffold and the amino group was further methylated to get constantly cationic-charged lipids. Lipids were synthesized in both configurations and as racemats, and the counterions were varied as well. Table 1 summarizes the structural features of these lipids. 

ImaRx/positively charged lipid sheU/plasmid DNA attached Ultrasound-activated DNA delivery [10]... 

The Helmholtz model was found not to be able to give a satisfactory analysis of measured data. Later, another theory of the diffuse double layer was proposed by Gouy and Chapman. The interfacial region for a system with charged lipid, R-Na+, with NaCl, is shown in Figure 4.10. 

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